Thioridazine protects the mouse from a virulent infection by Salmonella enterica serovar Typhimurium 74

Asish Dasgupta; Sayanti Mukherjee; Shaswati Chaki; Sujata G Dastidar; Oliver Hendricks; Jørn B Christensen; Jette E. Kristiansen; Leonard Amaral

doi:10.1016/j.ijantimicag.2009.09.027

Thioridazine protects the mouse from a virulent infection by Salmonella enterica serovar Typhimurium 74

Asish Dasgupta, Sayanti Mukherjee, Shaswati Chaki, Sujata G Dastidar, Oliver Hendricks, Jørn B Christensen, Jette E. Kristiansen, Leonard Amaral

Kemisk Institut

23 Citationer (Scopus)

Abstract

When administered to mice at doses of 100 μg/mouse and 200 μg/mouse, thioridazine (TDZ) significantly protected animals from the lethality produced by a virulent strain of Salmonella enterica serovar Typhimurium and reduced the number of bacteria retrieved from the spleen, liver and heart blood. The protection conferred by TDZ against a virulent Salmonella infection is hypothesised to be due to a reduction in the 55 kDa virulence protein of the outer membrane of the organism, as this protein is almost totally absent when the organism is exposed to the phenothiazine. It is further hypothesised that the reduction in the 55 kDa virulence factor renders the organism susceptible to the action of hydrolytic enzymes of the neutrophil phagolysosome, whereas in the absence of exposure to TDZ intracellular ingestion and localisation of the phagocytosed bacterium does not result in killing owing to rapid induction of the two-step PmrA/B regulon that results in the eventual synthesis and insertion of lipid A into the nascent lipopolysaccharide layer of the outer membrane.

Originalsprog	Engelsk
Tidsskrift	International Journal of Antimicrobial Agents
Vol/bind	35
Udgave nummer	2
Sider (fra-til)	174-6
Antal sider	3
ISSN	0924-8579
DOI	https://doi.org/10.1016/j.ijantimicag.2009.09.027
Status	Udgivet - 1 feb. 2010

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10.1016/j.ijantimicag.2009.09.027

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@article{147157610235482583a4bfb39e37ed83,

title = "Thioridazine protects the mouse from a virulent infection by Salmonella enterica serovar Typhimurium 74",

abstract = "When administered to mice at doses of 100 μg/mouse and 200 μg/mouse, thioridazine (TDZ) significantly protected animals from the lethality produced by a virulent strain of Salmonella enterica serovar Typhimurium and reduced the number of bacteria retrieved from the spleen, liver and heart blood. The protection conferred by TDZ against a virulent Salmonella infection is hypothesised to be due to a reduction in the 55 kDa virulence protein of the outer membrane of the organism, as this protein is almost totally absent when the organism is exposed to the phenothiazine. It is further hypothesised that the reduction in the 55 kDa virulence factor renders the organism susceptible to the action of hydrolytic enzymes of the neutrophil phagolysosome, whereas in the absence of exposure to TDZ intracellular ingestion and localisation of the phagocytosed bacterium does not result in killing owing to rapid induction of the two-step PmrA/B regulon that results in the eventual synthesis and insertion of lipid A into the nascent lipopolysaccharide layer of the outer membrane.",

keywords = "Animals, Anti-Infective Agents, Antibiotic Prophylaxis, Bacterial Proteins, Blood, Colony Count, Microbial, Liver, Male, Mice, Microbial Viability, Neutrophils, Salmonella Infections, Animal, Salmonella typhimurium, Spleen, Survival Analysis, Thioridazine, Virulence Factors",

author = "Asish Dasgupta and Sayanti Mukherjee and Shaswati Chaki and Dastidar, {Sujata G} and Oliver Hendricks and Christensen, {J{\o}rn B} and Kristiansen, {Jette E.} and Leonard Amaral",

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doi = "10.1016/j.ijantimicag.2009.09.027",

language = "English",

volume = "35",

pages = "174--6",

journal = "International Journal of Antimicrobial Agents",

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TY - JOUR

T1 - Thioridazine protects the mouse from a virulent infection by Salmonella enterica serovar Typhimurium 74

AU - Dasgupta, Asish

AU - Mukherjee, Sayanti

AU - Chaki, Shaswati

AU - Dastidar, Sujata G

AU - Hendricks, Oliver

AU - Christensen, Jørn B

AU - Kristiansen, Jette E.

AU - Amaral, Leonard

PY - 2010/2/1

Y1 - 2010/2/1

N2 - When administered to mice at doses of 100 μg/mouse and 200 μg/mouse, thioridazine (TDZ) significantly protected animals from the lethality produced by a virulent strain of Salmonella enterica serovar Typhimurium and reduced the number of bacteria retrieved from the spleen, liver and heart blood. The protection conferred by TDZ against a virulent Salmonella infection is hypothesised to be due to a reduction in the 55 kDa virulence protein of the outer membrane of the organism, as this protein is almost totally absent when the organism is exposed to the phenothiazine. It is further hypothesised that the reduction in the 55 kDa virulence factor renders the organism susceptible to the action of hydrolytic enzymes of the neutrophil phagolysosome, whereas in the absence of exposure to TDZ intracellular ingestion and localisation of the phagocytosed bacterium does not result in killing owing to rapid induction of the two-step PmrA/B regulon that results in the eventual synthesis and insertion of lipid A into the nascent lipopolysaccharide layer of the outer membrane.

AB - When administered to mice at doses of 100 μg/mouse and 200 μg/mouse, thioridazine (TDZ) significantly protected animals from the lethality produced by a virulent strain of Salmonella enterica serovar Typhimurium and reduced the number of bacteria retrieved from the spleen, liver and heart blood. The protection conferred by TDZ against a virulent Salmonella infection is hypothesised to be due to a reduction in the 55 kDa virulence protein of the outer membrane of the organism, as this protein is almost totally absent when the organism is exposed to the phenothiazine. It is further hypothesised that the reduction in the 55 kDa virulence factor renders the organism susceptible to the action of hydrolytic enzymes of the neutrophil phagolysosome, whereas in the absence of exposure to TDZ intracellular ingestion and localisation of the phagocytosed bacterium does not result in killing owing to rapid induction of the two-step PmrA/B regulon that results in the eventual synthesis and insertion of lipid A into the nascent lipopolysaccharide layer of the outer membrane.

KW - Animals

KW - Anti-Infective Agents

KW - Antibiotic Prophylaxis

KW - Bacterial Proteins

KW - Blood

KW - Colony Count, Microbial

KW - Liver

KW - Male

KW - Mice

KW - Microbial Viability

KW - Neutrophils

KW - Salmonella Infections, Animal

KW - Salmonella typhimurium

KW - Spleen

KW - Survival Analysis

KW - Thioridazine

KW - Virulence Factors

U2 - 10.1016/j.ijantimicag.2009.09.027

DO - 10.1016/j.ijantimicag.2009.09.027

M3 - Journal article

C2 - 20005679

SN - 0924-8579

VL - 35

SP - 174

EP - 176

JO - International Journal of Antimicrobial Agents

JF - International Journal of Antimicrobial Agents

IS - 2

ER -

Thioridazine protects the mouse from a virulent infection by Salmonella enterica serovar Typhimurium 74

Abstract

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